CN103467319B - Method for synthesizing beta-amino-carbonyl compound by pure water phase - Google Patents
Method for synthesizing beta-amino-carbonyl compound by pure water phase Download PDFInfo
- Publication number
- CN103467319B CN103467319B CN201310421972.3A CN201310421972A CN103467319B CN 103467319 B CN103467319 B CN 103467319B CN 201310421972 A CN201310421972 A CN 201310421972A CN 103467319 B CN103467319 B CN 103467319B
- Authority
- CN
- China
- Prior art keywords
- phenyl
- pimelinketone
- catalyzer
- replaced
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for synthesizing a beta-amino-carbonyl compound by a pure water phase. Water is used as a reacting solvent, aldehydes, amines and ketones are used as raw materials, and salicylic acid or salicylic acid derivatives is or are adopted as a catalyst to react. The method opens a new low-cost, green and effective way to the preparation of beta-amino-carbonyl compounds, and has the advantages that a target product is good in selectivity and high in yield; the catalyst is small in dose and does not need to be separated from the solvent after the reaction is completed, and can be recycled directly in an aqueous solution manner; experiment results prove that the catalyst still has high catalytic activity after being recycled for 5 times, and the yield of the product is basically the same.
Description
Technical field
The invention belongs to catalysis technical field of organic synthesis, be specifically related to that a kind of to take Whitfield's ointment or salicylic derivative be catalyzer, the method for synthetic beta-amino carbonyl compound.
Background technology
Beta-amino carbonyl compound is the key intermediate of synthetic drugs and natural product (beta-alkamine, beta-amino acids, beta-lactam etc.), has extensive use in organic synthesis.By beta-amino carbonyl compound, can obtain polytype compound.Beta-amino carbonyl compound is also the important biologically active substance of a class, has the multiple biological activitys such as cough-relieving, antibacterial, anti-inflammatory, anticancer, antiviral, calm, pain relieving, step-down, inhibition oedema, anticoagulation.From the angle of environment protection, energy-conservation and Atom economy, with the direct efficient selective of not activated aldehyde, amine and ketone, build beta-amino carbonyl compound and have much magnetism.And the method for this direct construction needs desirable suitable catalystic converter system to realize.
At present synthetic beta-amino carbonyl compound catalyzer used comprises the catalyzer that contains metallic element and the catalyzer of containing metal element not.The catalyzer that contains metal mainly comprises following a few class: metal Lewis acid catalyst, metal heteropolyacid catalyst and metal oxide nanoparticles catalyzer, its maximum defect is that high toxicity has caused very big impact to environment, and its reaction process often need to be carried out in organic solvent, has run counter to especially the fundamental principle of Green Chemistry.Therefore, can adopt metal-free catalyzer in pure aquatic system, to realize the synthetic of beta-amino carbonyl compound is subject to the people's attention.Metal-free catalyzer can be divided into inorganic acid catalyst and organic acid catalyst.Inorganic acid catalyst (for example HCl, H
2sO
4) to realize synthetic beta-amino carbonyl compound efficiently, in reaction system, must have a certain amount of tensio-active agent, but the existence of tensio-active agent makes product separation process too complicated.And organic acid can be avoided this problem just, do not need the existence of tensio-active agent just can contact preferably with reactant, there is good catalytic effect.But most organic acid catalyst all exists some problems, as catalyst levels is large, need reactant molar weight more than 20%; Long reaction time, needs reaction more than 18 hours; Etc..In addition, realize recycling of catalyzer and concerning most of organic acid catalysts, have huge challenge.
Summary of the invention
Technical problem to be solved by this invention is to overcome the shortcoming that existing beta-amino carbonyl compound preparation method exists, and provides that a kind of catalyst levels is few, catalytic activity is high and the pure water phase synthesis method of reusable beta-amino carbonyl compound.
Solving the problems of the technologies described above adopted technical scheme is: using water as reaction solvent, aromatic aldehyde is mixed for 1:1～1.5:1～2 in molar ratio with aromatic amine, aliphatic ketone or aromatic ketone, the catalyzer that adds aromatic aldehyde molar weight 5%～10%, normal-temperature reaction 3～12 hours, filtering separation, solid obtains beta-amino carbonyl compound through column chromatography purifying, and the aqueous solution that is dissolved with catalyzer is reused.
Above-mentioned catalyzer is Whitfield's ointment or salicylic derivative.
Mol ratio the best of aromatic aldehyde of the present invention and aromatic amine, aliphatic ketone or aromatic ketone is 1:1.1:1.5.
Above-mentioned aromatic aldehyde specifically can be selected any one in phenyl aldehyde, 4-chloro-benzaldehyde, aubepine, paranitrobenzaldehyde, NSC 43794, m-nitrobenzaldehyde, o-chlorobenzaldehyde, o-methoxybenzaldehyde; Aromatic amine specifically can be selected any one in aniline, p-Chlorobenzoic acid amide, p-Nitroaniline, para-totuidine, P-nethoxyaniline, meta-aminotoluene, m-chloro aniline, Ortho-Chloro aniline, ORTHO ANISIDINE; Aliphatic ketone specifically can be selected pimelinketone or propione, and aromatic ketone specifically can be selected methyl phenyl ketone or p-methoxy-acetophenone; Salicylic derivative specifically can be selected 5-sulphosalicylic acid, 5-NITROSALICYLIC ACID, 3, any one in 5-dinitrosalicylic acid, 5 bromosalicylic acid, para-aminosalicylic acid, 5-methoxyl group Whitfield's ointment, 5-chloro-salicylic acid.
The present invention be take water as solvent, low cost and environmental protection, take Whitfield's ointment or salicylic derivative is catalyzer, catalyst levels is few, does not need catalyzer separation from solvent after reaction finishes, and catalyzer can directly reuse with aqueous solution form, the results show, after reusing 5 times, its catalytic activity is still very high, and the yield of product is substantially constant, and product is easily separated, selectivity good, productive rate is high.
Embodiment
Below in conjunction with embodiment, the present invention is described in more detail, but the invention is not restricted to these embodiment.
Embodiment 1
Synthetic 2-[(4-chloro-phenyl-) (4-chloroanilino) methyl]-pimelinketone
In 10mL round-bottomed flask, add 0.0218g (0.1mmol) 5-sulphosalicylic acid, 0.2810g (2mmol) 4-chloro-benzaldehyde, 0.2805g (2.2mmol) p-Chlorobenzoic acid amide, 309 μ L (3mmol) pimelinketone, add again 2mL distilled water, stir, normal-temperature reaction 3 hours, filtering separation, solid obtains 2-[(4-chloro-phenyl-through column chromatography separating purification) (4-chloroanilino) methyl]-pimelinketone, its productive rate is 94%, along inverse ratio, be 33:67, the spectral data of product is:
1h NMR (400MHz, CDCl
3) δ ppm:7.31-7.24 (m, 4H), 7.04-6.98 (m, 2H), 6.42 (d, J=8.8Hz, 2H), 4.79 (s, 1H), 4.52 (d, J=6.2Hz, 1H), 2.72 (dd, J=8.7,4.9Hz, 1H), 2.45-2.27 (m, 2H), 2.05-1.83 (m, 3H), 1.83-1.62 (m, 3H);
13c NMR (101MHz, CDCl
3) δ ppm:211.29,144.64,138.88,131.92,127.93,127.67,127.60,121.37,113.75,56.81,56.18,41.17,30.68,26.84,23.12.
In the filtrate obtaining after filtering, add 0.2810g (2mmol) 4-chloro-benzaldehyde, 0.2805g (2.2mmol) p-Chlorobenzoic acid amide, 309 μ L (3mmol) pimelinketone, mix, stir, normal-temperature reaction 3 hours, filtering separation, solid product column chromatography separating purification, filtrate is reused.Catalyzer reuse number of times on the impact of products collection efficiency in Table 1.
Table 1 catalyzer is reused the impact of number of times on products collection efficiency
| Access times (inferior) | 1 | 2 | 3 | 4 | 5 |
| Productive rate (%) | 94 | 95 | 92 | 94 | 93 |
From table 1,5-sulphosalicylic acid is reused after 5 times, and the productive rate of product is substantially constant, illustrates that catalyst activity is high, reuses its catalytic activity impact little.
Embodiment 2
Synthetic 2-[(phenyl) (anilino) methyl]-pimelinketone
In embodiment 1,4-chloro-benzaldehyde used is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar aniline, other steps are identical with embodiment 1, obtain 2-[(phenyl) (anilino) methyl]-pimelinketone, its productive rate is 90%, along inverse ratio, be 18:82, catalyzer is reused 5 times, 2-[(phenyl) (anilino) methyl] productive rate of-pimelinketone still can reach 88%, and its spectral data is:
1h NMR (400MHz, CDCl
3) δ ppm:7.42-7.36 (m, 2H), 7.31 (d, J=7.1Hz, 2H), 7.24-7.18 (m, 1H), 7.06 (t, J=6.9Hz, 2H), 6.63 (t, J=7.2Hz, 1H), 6.54 (d, J=7.6Hz, 2H), 4.72 (dd, J=71.2,5.2Hz, 2H), 2.88-2.29 (m, 2H), 1.90 (dd, J=17.1,9.1Hz, 6H), 1.80-1.68 (m, 1H);
13c NMR (101MHz, CDCl
3) δ ppm:212.33,146.01,140.21,127.96,127.58,126.26,125.84,116.64,112.63,58.22,51.25,49.84,34.50,10.55,6.48,6.38.
Embodiment 3
Synthetic 2-[(phenyl) (anilino) methyl]-pimelinketone
In embodiment 1,5-sulphosalicylic acid used is replaced with equimolar Whitfield's ointment, 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar aniline, and other steps are identical with embodiment 1, obtain 2-[(phenyl) (anilino) methyl]-pimelinketone, its productive rate is 80%, along inverse ratio, be 30:70, catalyzer is reused 5 times, 2-[(phenyl) (anilino) methyl] productive rate of-pimelinketone is substantially constant.
Embodiment 4
Synthetic 2-[(phenyl) (anilino) methyl]-pimelinketone
In embodiment 1,5-sulphosalicylic acid used is replaced with equimolar 5-NITROSALICYLIC ACID, 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar aniline, and other steps are identical with embodiment 1, obtain 2-[(phenyl) (anilino) methyl]-pimelinketone, its productive rate is 85%, along inverse ratio, be 30:70, catalyzer is reused 5 times, 2-[(phenyl) (anilino) methyl] productive rate of-pimelinketone is substantially constant.
Embodiment 5
Synthetic 2-[(phenyl) (anilino) methyl]-pimelinketone
In embodiment 1,5-sulphosalicylic acid used is with equimolar 3,5-dinitrosalicylic acid is replaced, and 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, and p-Chlorobenzoic acid amide is replaced with equimolar aniline, other steps are identical with embodiment 1, obtain 2-[(phenyl) (anilino) methyl]-pimelinketone, its productive rate is 83%, along inverse ratio, is 35:65, catalyzer is reused 5 times, 2-[(phenyl) (anilino) methyl] productive rate of-pimelinketone is substantially constant.
Embodiment 6
Synthetic 2-[(phenyl) (anilino) methyl]-pimelinketone
In embodiment 1,4-chloro-benzaldehyde used is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with the aniline of 3mmol, the pimelinketone of 3mmol is replaced with the pimelinketone of 4mmol, and other steps are identical with embodiment 1, obtain 2-[(phenyl) (anilino) methyl]-pimelinketone, its productive rate is 92%, along inverse ratio, be 34:66, catalyzer is reused 5 times, 2-[(phenyl) (anilino) methyl] productive rate of-pimelinketone is substantially constant.
Embodiment 7
Synthetic 2-[(phenyl) (anilino) methyl]-pimelinketone
In embodiment 1,4-chloro-benzaldehyde used is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with the aniline of 2mmol, the pimelinketone of 3mmol is replaced with the pimelinketone of 2mmol, and other steps are identical with embodiment 1, obtain 2-[(phenyl) (anilino) methyl]-pimelinketone, its productive rate is 58%, along inverse ratio, be 38:62, catalyzer is reused 5 times, 2-[(phenyl) (anilino) methyl] productive rate of-pimelinketone is substantially constant.
Embodiment 8
Synthetic 2-[(phenyl) (anilino) methyl]-pimelinketone
In embodiment 1,4-chloro-benzaldehyde used is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with the aniline of 2mmol, the pimelinketone of 3mmol is replaced with the pimelinketone of 4mmol, and other steps are identical with embodiment 1, obtain 2-[(phenyl) (anilino) methyl]-pimelinketone, its productive rate is 78%, along inverse ratio, be 35:65, catalyzer is reused 5 times, 2-[(phenyl) (anilino) methyl] productive rate of-pimelinketone is substantially constant.
Embodiment 9
Synthetic 2-[(4-nitrophenyl) (anilino) methyl]-pimelinketone
In embodiment 1,5-sulphosalicylic acid used is replaced with equimolar 5-chloro-salicylic acid, 4-chloro-benzaldehyde is replaced with equimolar paranitrobenzaldehyde, p-Chlorobenzoic acid amide is replaced with equimolar aniline, other steps are identical with embodiment 1, obtain 2-[(4-nitrophenyl) (anilino) methyl]-pimelinketone, its productive rate is 82%, along inverse ratio, be 56:44, catalyzer is reused 5 times, 2-[(4-nitrophenyl) (anilino) methyl] productive rate of-pimelinketone is substantially constant, and the spectral data of product is:
1h NMR (400MHz, CDCl
3) δ ppm:8.07 (d, J=8.6Hz, 2H), 7.49 (t, J=7.9Hz, 2H), 7.01 (t, J=7.7Hz, 2H), 6.63-6.56 (m, 1H), 6.42 (d, J=7.9Hz, 2H), 4.78 (s, 1H), 4.64 (d, J=5.1Hz, 1H), 2.77 (dd, J=9.2,4.5Hz, 1H), 2.39-2.19 (m, 2H), 1.96 (dd, J=14.5,8.5Hz, 2H), 1.86 (d, J=5.6Hz, 1H), 1.74-1.51 (m, 3H);
13c NMR (101MHz, CDCl
3) δ ppm:211.68,149.85,146.70,129.28,128.25,123.67,118.15,113.53,99.99,57.84,57.06,42.42,32.01,27.76,24.50.
Embodiment 10
Synthetic 2-[(phenyl) (4-oil of mirbane amido) methyl]-pimelinketone
In embodiment 1,4-chloro-benzaldehyde used is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar p-Nitroaniline, other steps are identical with embodiment 1, obtain 2-[(phenyl) (4-oil of mirbane amido) methyl]-pimelinketone, its productive rate is 93%, along inverse ratio, be 67:33, catalyzer is reused 5 times, 2-[(phenyl) (4-oil of mirbane amido) methyl] productive rate of-pimelinketone is substantially constant, and the spectral data of product is:
1h NMR (400MHz, CDCl
3) δ ppm:7.99 (d, J=7.9Hz, 2H), 7.34 (s, 5H), 6.52 (d, J=7.7Hz, 2H), 5.77 (s, 1H), 4.81 (d, J=83.0Hz, 1H), 2.90 (d, J=5.1Hz, 1H), 2.42 (t, J=15.6Hz, 2H), 2.06 (s, 2H), 1.92 (s, 2H), 1.74-1.60 (m, 2H);
13c NMR (101MHz, CDCl
3) δ ppm:211.06,152.80,139.84,138.12,128.68,127.63,127.43,126.15,112.22,56.99,55.70,42.28,28.63,26.64,24.69.
Embodiment 11
Synthetic 2-[(2-p-methoxy-phenyl) (anilino) methyl]-pimelinketone
In embodiment 1, the 5-sulphosalicylic acid of 0.1mmol used is replaced with the 5-sulphosalicylic acid of 0.2mmol, 4-chloro-benzaldehyde is replaced with equimolar o-methoxybenzaldehyde, p-Chlorobenzoic acid amide is replaced with equimolar aniline, reaction times is extended for 7 hours, other steps are identical with embodiment 1, obtain 2-[(2-p-methoxy-phenyl) (anilino) methyl]-pimelinketone, its productive rate is 88%, along inverse ratio, be 3:97, catalyzer is reused 5 times, and its productive rate is substantially constant, and the spectral data of product is:
1h NMR (400MHz, CDCl
3) δ ppm:7.27 (dd, J=7.5,1.4Hz, 1H), 7.09 (td, J=8.0,1.6Hz, 1H), 6.97 (dd, J=8.3,7.5Hz, 2H), 6.89-6.73 (m, 2H), 6.63-6.41 (m, 3H), 4.92 (d, J=7.1Hz, 1H), 4.81 (s, 1H), 3.83 (s, 3H), 2.77 (dd, J=12.7,7.0Hz, 1H), 2.40-2.29 (m, 1H), 2.21 (td, J=8.3,4.7Hz, 1H), 1.91-1.74 (m, 4H), 1.72-1.57 (m, 2H);
13c NMR (101MHz, CDCl
3) δ ppm:212.65,156.20,146.36,128.45,128.00,127.20,127.00,119.79,116.19,112.41,109.20,55.00,54.35,51.49,40.81,30.70,27.19,22.63.
Embodiment 12
Synthetic 2-[(phenyl) (3-toluidine) methyl]-pimelinketone
In embodiment 1, the 5-sulphosalicylic acid of 0.1mmol used is replaced with the 5-methoxyl group Whitfield's ointment of 0.2mmol, 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar meta-aminotoluene, reaction times is extended for 7 hours, other steps are identical with embodiment 1, obtain 2-[(phenyl) (3-toluidine) methyl]-pimelinketone, its productive rate is 70%, along inverse ratio, be 0:100, catalyzer is reused 5 times, 2-[(phenyl) (3-toluidine) methyl] productive rate of-pimelinketone is substantially constant, and its spectral data is:
1h NMR (400MHz, CDCl
3) δ ppm:7.36-7.24 (m, 2H), 7.19 (t, J=7.5Hz, 2H), 7.15-7.06 (m, 1H), 6.85 (t, J=7.8Hz, 1H), 6.41-6.20 (m, 3H), 4.57 (s, 1H), 4.53 (m, 1H), 2.65 (dd, J=7.1,5.4Hz, 1H), 2.36-2.15 (m, 2H), 2.09 (s, 3H), 2.04-1.68 (m, 4H), 1.59 (ddd, J=10.3,8.5,2.6Hz, 2H);
13c NMR (101MHz, CDCl
3) δ ppm:211.70,46.25,140.85,137.69,127.90,127.40,126.20,126.06,117.44,113.52,109.48,56.85,56.46,40.68,30.19,26.83,22.58,20.52.
Embodiment 13
Synthetic 2-[(3-nitrophenyl) (anilino) methyl]-pimelinketone
In embodiment 1, the 5-sulphosalicylic acid of 0.1mmol used is replaced with the para-aminosalicylic acid of 0.2mmol, 4-chloro-benzaldehyde is replaced with equimolar m-nitrobenzaldehyde, p-Chlorobenzoic acid amide is replaced with equimolar aniline, reaction times is extended for 7 hours, other steps are identical with embodiment 1, obtain 2-[(3-nitrophenyl) (anilino) methyl]-pimelinketone, its productive rate is 67%, along inverse ratio, be 40:60, catalyzer is reused 5 times, and its productive rate is substantially constant, and the spectral data of product is:
1h NMR (400MHz, CDCl
3) δ ppm:8.24 (dd, J=5.8, 4.0Hz, 1H), 8.07 (ddd, J=8.1, 2.3, 0.8Hz, 1H), 7.77 (dd, J=4.6, 3.1Hz, 1H), 7.46 (t, J=7.9Hz, 1H), 7.08 (dd, J=11.8, 4.1Hz, 2H), 6.70-6.64 (m, 1H), 6.56-6.50 (m, 2H), 4.72 (d, J=5.1Hz, 1H), 4.63 (s, 1H), 2.87 (dd, J=8.2, 4.4Hz, 1H), 2.47-2.28 (m, 2H), 2.14-2.01 (m, 2H), 1.94 (dd, J=6.0, 1.8Hz, 1H), 1.77 (ddd, J=15.4, 6.8, 2.8Hz, 1H), 1.66-1.58 (m, 2H),
13c NMR (101MHz, CDCl
3) δ ppm:209.68,147.41,145.62,143.15,133.15,128.26,128.18,121.51,121.23,117.31,113.00,56.11,55.27,41.45,28.29,26.09,23.91.
Embodiment 14
Synthetic 2-[(phenyl) (3-chloroanilino) methyl]-pimelinketone
In embodiment 1, the 5-sulphosalicylic acid of 0.1mmol used is replaced with the para-aminosalicylic acid of 0.2mmol, and 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, and p-Chlorobenzoic acid amide is replaced with equimolar m-chloro aniline, reaction times is extended for 7 hours, other steps are identical with embodiment 1, obtain 2-[(phenyl) (3-chloroanilino) methyl]-pimelinketone, its productive rate is 68%, along inverse ratio, be 55:45, catalyzer is reused 5 times, and its productive rate is substantially constant, and the spectral data of product is:
1h NMR (400MHz, CDCl
3) δ ppm:7.39-7.27 (m, 4H), 7.25-7.19 (m, 1H), 6.96 (td, J=8.0,3.6Hz, 1H), 6.60 (t, J=7.5Hz, 1H), 6.53 (dt, J=10.1,2.1Hz, 1H), 6.41 (dt, J=3.8,2.2Hz, 1H), 4.66 (dd, J=82.0,5.5Hz, 2H), 2.85-2.71 (m, 1H), 2.49-2.25 (m, 2H), 2.08-1.57 (m, 6H);
13c NMR (101MHz, CDCl
3) δ ppm:211.18,148.52,141.21,134.72,130.00,128.49,127.35,127.15,117.58,113.82,111.85,57.35,56.33,42.01,28.66,26.88,23.89.
Embodiment 15
Synthetic 2-[(phenyl) (2-chloroanilino) methyl]-pimelinketone
In embodiment 1, the 5-sulphosalicylic acid of 0.1mmol used is replaced with the 5-sulphosalicylic acid of 0.2mmol, 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar Ortho-Chloro aniline, reaction times is extended for 7 hours, other steps are identical with embodiment 1, obtain 2-[(phenyl) (2-chloroanilino) methyl]-pimelinketone, its productive rate is 94%, along inverse ratio, be 5:95, catalyzer is reused 5 times, 2-[(phenyl) (2-chloroanilino) methyl] productive rate of-pimelinketone is substantially constant, and its spectral data is:
1h NMR (400MHz, CDCl
3) δ ppm:7.39-7.35 (m, 2H), 7.33-7.28 (m, 2H), 7.25-7.18 (m, 2H), 6.97-6.91 (m, 1H), 6.55 (td, J=7.7,1.4Hz, 1H), 6.47 (dd, J=8.2,1.2Hz, 1H), 5.39 (s, 1H), 4.71 (s, 1H), 2.90-2.78 (m, 1H), 2.47-2.31 (m, 2H), 2.02-1.87 (m, 3H), 1.84-1.65 (m, 3H);
13c NMR (101MHz, CDCl
3) δ ppm:211.94,143.21,141.11,129.05,128.50,127.52,127.28,127.23,119.74,117.40,112.31,57.83,57.41,42.10,31.57,27.88,24.14.
Embodiment 16
Synthetic 2-methyl isophthalic acid-phenyl-1-(4-toluidine)-propione
In embodiment 1, the 5-sulphosalicylic acid of 0.1mmol used is replaced with the 5-sulphosalicylic acid of 0.2mmol, 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar para-totuidine, pimelinketone is replaced with propione, reaction times is extended for 11 hours, other steps are identical with embodiment 1, obtain 2-methyl isophthalic acid-phenyl-1-(4-toluidine)-propione, its productive rate is that 71%(is cis-product, without trans product), catalyzer is reused 5 times, the productive rate of 2-methyl isophthalic acid-phenyl-1-(4-toluidine)-propione is substantially constant, its spectral data is:
1h NMR (400MHz, CDCl
3) δ ppm:7.26 (s, 1H), 7.26-7.13 (m, 4H), 6.84 (d, J=5.7Hz, 2H), 6.37 (d, J=5.0Hz, 2H), 4.60 (s, 1H), 4.16 (s, 1H), 2.96 (d, J=5.6Hz, 1H), 2.31 (dtd, J=14.4,7.2,3.7Hz, 2H), 2.12 (s, 3H), 1.05 (dd, J=6.9,3.6Hz, 3H), 0.94-0.84 (m, 3H),
13c NMR (101MHz, CDCl
3) δ ppm:213.32,144.73,141.40,129.56,128.56,127.19,126.85,126.81,113.73,59.43,52.29,35.46,20.30,11.46,7.52.
Embodiment 17
Synthetic 1-phenyl-3-phenyl-3-(anilino)-1-acetone
In embodiment 1, the 5-sulphosalicylic acid of 0.1mmol used is replaced with the 5-sulphosalicylic acid of 0.2mmol, 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar aniline, pimelinketone is replaced with equimolar methyl phenyl ketone, reaction times is extended for 12 hours, other steps are identical with embodiment 1, obtain 1-phenyl-3-phenyl-3-(anilino)-1-acetone, its productive rate is 53%, catalyzer is reused 5 times, and 1-phenyl-3-phenyl-3-(anilino)-1-acetone productive rate is substantially constant, and its spectral data is:
1h NMR (400MHz, CDCl
3) δ ppm:7.90 (d, J=7.2Hz, 2H), 7.56 (t, J=7.3Hz, 1H), 7.42-7.46 (m, 4H), 7.32 (t, J=7.3Hz, 2H), 7.21-7.25 (m, 1H), 7.09 (t, J=7.9Hz, 2H), 6.69 (t, J=7.3Hz, 1H), 6.59 (d, J=8.0Hz, 2H), 5.00 (dd, J=7.2,5.7Hz, 1H), 3.54 (dd, J=16.1,5.4Hz, 1H), 3.47 (dd, J=16.1,7.7Hz, 1H);
13c NMR (101MHz, CDCl
3) δ ppm:198.4,146.8,142.9,136.9,133.7,129.3,129.0,128.9,128.4,127.6,126.7,118.3,114.3,55.3,46.4.
Embodiment 18
Synthetic 1-(4-p-methoxy-phenyl)-3-phenyl-3-(anilino)-1-acetone
In embodiment 1, the 5-sulphosalicylic acid of 0.1mmol used is replaced with the 5-sulphosalicylic acid of 0.2mmol, 4-chloro-benzaldehyde is replaced with equimolar phenyl aldehyde, p-Chlorobenzoic acid amide is replaced with equimolar aniline, pimelinketone is replaced with equimolar p-methoxy-acetophenone, reaction times is extended for 12 hours, other steps are identical with embodiment 1, obtain 1-(4-p-methoxy-phenyl)-3-phenyl-3-(anilino)-1-acetone, its productive rate is 40%, catalyzer is reused 5 times, the productive rate of 1-(4-p-methoxy-phenyl)-3-phenyl-3-(anilino)-1-acetone is substantially constant, its spectral data is:
1h NMR (400MHz, CDCl
3) δ ppm:7.81 (d, J=8.9Hz, 2H), 7.36 (d, J=7.4Hz, 2H), 7.24 (t, J=7.5Hz, 2H), 7.16 (dd, J=13.4,6.1Hz, 1H), 7.00 (dd, J=8.4,7.5Hz, 2H), 6.83 (d, J=8.9Hz, 2H), 6.57 (t, J=7.3Hz, 1H), 6.47 (d, J=7.7Hz, 2H), 4.89 (dd, J=7.6,5.1Hz, 1H), 4.53 (s, 1H), 3.78 (s, 3H), 3.32 (ddd, J=23.6,15.8,6.4Hz, 2H),
13c NMR (101MHz, CDCl
3) δ ppm:196.77,163.77,147.10,143.18,130.56,129.85,129.07,128.80,127.28,126.36,117.69,113.85,113.82,55.50,55.06,46.00.
Claims (1)
1. the pure water phase synthesis method of a beta-amino carbonyl compound, it is characterized in that: using water as reaction solvent, by aromatic aldehyde with aromatic amine, aliphatic ketone in molar ratio for 1:1.1:1.5 mixes, the catalyzer that adds aromatic aldehyde molar weight 5%～10%, normal-temperature reaction 3～12 hours, filtering separation, solid obtains beta-amino carbonyl compound through column chromatography purifying, and the aqueous solution that is dissolved with catalyzer is reused;
Above-mentioned aromatic aldehyde is any one in phenyl aldehyde, 4-chloro-benzaldehyde, aubepine, paranitrobenzaldehyde, NSC 43794, m-nitrobenzaldehyde, o-chlorobenzaldehyde, o-methoxybenzaldehyde; Described aromatic amine is any one in aniline, p-Chlorobenzoic acid amide, p-Nitroaniline, para-totuidine, P-nethoxyaniline, meta-aminotoluene, m-chloro aniline, Ortho-Chloro aniline, ORTHO ANISIDINE; Described aliphatic ketone is pimelinketone or propione; Described catalyzer is any one in Whitfield's ointment, 5-sulphosalicylic acid, 5-NITROSALICYLIC ACID, 5-methoxyl group Whitfield's ointment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310421972.3A CN103467319B (en) | 2013-09-16 | 2013-09-16 | Method for synthesizing beta-amino-carbonyl compound by pure water phase |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310421972.3A CN103467319B (en) | 2013-09-16 | 2013-09-16 | Method for synthesizing beta-amino-carbonyl compound by pure water phase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103467319A CN103467319A (en) | 2013-12-25 |
| CN103467319B true CN103467319B (en) | 2014-10-15 |
Family
ID=49792400
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310421972.3A Expired - Fee Related CN103467319B (en) | 2013-09-16 | 2013-09-16 | Method for synthesizing beta-amino-carbonyl compound by pure water phase |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103467319B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104496831B (en) * | 2014-12-30 | 2016-08-24 | 陕西师范大学 | The method of beta-amino carbonyl compound is prepared in graphene oxide catalysis |
| CN104876829B (en) * | 2015-05-27 | 2016-08-24 | 陕西师范大学 | The method of beta-amino carbonyl compound is prepared in polyacrylic acid heterogeneous catalysis |
-
2013
- 2013-09-16 CN CN201310421972.3A patent/CN103467319B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN103467319A (en) | 2013-12-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zolfigol et al. | Design of ionic liquid 1, 3-disulfonic acid imidazolium hydrogen sulfate as a dual-catalyst for the one-pot multi-component synthesis of 1, 2, 4, 5-tetrasubstituted imidazoles | |
| Karami et al. | Novel silica tungstic acid (STA): Preparation, characterization and its first catalytic application in synthesis of new benzimidazoles | |
| Zeng et al. | One-pot three-component Mannich-type reactions using Sulfamic acid catalyst under ultrasound irradiation | |
| Ollevier et al. | Direct-type catalytic three-component Mannich reaction in aqueous media | |
| Kadam et al. | Graphite catalyzed green synthesis of quinoxalines | |
| Shaterian et al. | Synthesis of benzoxanthene derivatives using Brønsted acidic ionic liquids (BAILs), 2-pyrrolidonium hydrogen sulfate and (4-sulfobutyl) tris (4-sulfophenyl) phosphonium hydrogen sulfate | |
| Ghorbani-Vaghei et al. | Efficient and solvent-free synthesis of 1-amidoalkyl-2-naphthols using N, N, N’, N’-tetrabromobenzene-1, 3-disulfonamide | |
| Kumar et al. | Solid-supported ruthenium (0): an efficient heterogeneous catalyst for hydration of nitriles to amides under microwave irradiation | |
| Wang et al. | Cyclic phosphoric acid catalyzed one-pot, four-component synthesis of 1, 2, 4, 5-tetrasubstituted imidazoles | |
| Mansoor et al. | Aqua-mediated synthesis of acridinediones with reusable silica-supported sulfuric acid as an efficient catalyst | |
| Mohammadpoor-Baltork et al. | Silica sulfuric acid: A versatile and reusable heterogeneous catalyst for the synthesis of oxazolines and imidazolines under various reaction conditions | |
| Aswin et al. | An efficient one-pot synthesis of 1, 4-dihydropyridine derivatives through Hantzsch reaction catalysed by melamine trisulfonic acid | |
| Kalantari | Synthesis of 1, 8-dioxo-octahydroxanthenes and bis (indolyl) methanes catalyzed by [Et3NH][H2PO4] as a cheap and mild acidic ionic liquid | |
| CN103467319B (en) | Method for synthesizing beta-amino-carbonyl compound by pure water phase | |
| CN103467321B (en) | Method for preparing beta-amino-carbonyl compound | |
| CN102757346A (en) | Preparation method of dimethyl fumarate | |
| Dong et al. | Knoevenagel condensation catalysed by poly (vinyl chloride) supported tetraethylenepentamine (PVC-TEPA) | |
| CN110372611A (en) | A kind of method of the polysubstituted dihydroquinazoline ketone of selectivity synthesis or quinazolinone | |
| Nagrik et al. | One-pot preparation of β–amino carbonyl compounds by Mannich reaction using MgO/ZrO2 as effective and reusable catalyst | |
| CN101914060B (en) | Synthesis of polyhydroacridine derivatives by clean catalysis of degradable ionic liquid | |
| CN104140374B (en) | The method of poly-amino phenol and cyclopentadienyl titanium dichloride heterogeneous catalysis synthesis beta-amino carbonyl compound | |
| CN101260068A (en) | Method for preparing methyl 4-(4'-aminophenylmethylene)phenylaminoformate | |
| Krishnan et al. | Aminated poly (vinyl chloride): An efficient green catalyst for Knoevenagel condensation reactions | |
| CN107721936A (en) | The method of the ketone compounds of 3,4 dihydro-pyrimidin of synthesis in water 2 | |
| Cai et al. | One-pot multi-component synthesis of amidoalkyl naphthols with potassium hydrogen sulfate as catalyst under solvent-free condition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141015 Termination date: 20170916 |